[SP6-3D-7] Five-methyltetrahydrofolate in the Cerebrospinal Fluid of Pediatric Patients with Inborn Errors of Metabolism Affecting Folate Metabolism and Transport
[Introduction] Five-methyltetrahydrofolate (5-MTHF) is required in purine and thymidylate biosynthesis and DNA methylation. We developed an assay system of 5-MTHF in the cerebrospinal fluid (CSF) of pediatric patients. We show the utility of this assay in inborn errors of metabolism that affect folate metabolism and transport across the blood-CSF barrier.
[Methodology] CSF samples were prospectively collected since May 2012 at Okayama University Hospital and other hospitals in Japan from pediatric patients who underwent lumbar puncture to investigate their neurological symptoms. This study was approved by the ethics committee of Okayama University Hospital. CSF 5-MTHF was measured by high-performance liquid chromatography with fluorescence detection (Clin Chim Acta 2016;460:120-5). CSF 5-MTHF concentrations of patients with known disorders affecting folate metabolism and transport were compared with reference values established at our laboratory.
[Results] CSF 5-MTHF concentrations were determined in a total of 290 patients. There were three patients with folate receptor alpha (FRα) defect (primary cerebral folate deficiency; CFD), one patient with Kearns-Sayre syndrome (KSS) (secondary CFD), and one patient with methylentetrahydrofolate reductase (MTHFR) deficiency (5-MTHF biosynthesis defect). These patients had remarkably low concentrations of CSF 5-MTHF (<4 nmol/L). Folinic acid supplementation for the patients with FRα defect normalized CSF 5-MTHF (>25 nmol/L) and resulted in clinical improvement. Although folic acid therapy for the patient with KSS moderately increased CSF 5-MTHF (22.7 nmol/L), the patient with MTHFR deficiency showed no increase in 5-MTHF.
[Conclusions] The assay of 5-MTHF is helpful in the diagnosis and evaluation of treatment in CFD and 5-MTHF biosynthesis defect.
[Methodology] CSF samples were prospectively collected since May 2012 at Okayama University Hospital and other hospitals in Japan from pediatric patients who underwent lumbar puncture to investigate their neurological symptoms. This study was approved by the ethics committee of Okayama University Hospital. CSF 5-MTHF was measured by high-performance liquid chromatography with fluorescence detection (Clin Chim Acta 2016;460:120-5). CSF 5-MTHF concentrations of patients with known disorders affecting folate metabolism and transport were compared with reference values established at our laboratory.
[Results] CSF 5-MTHF concentrations were determined in a total of 290 patients. There were three patients with folate receptor alpha (FRα) defect (primary cerebral folate deficiency; CFD), one patient with Kearns-Sayre syndrome (KSS) (secondary CFD), and one patient with methylentetrahydrofolate reductase (MTHFR) deficiency (5-MTHF biosynthesis defect). These patients had remarkably low concentrations of CSF 5-MTHF (<4 nmol/L). Folinic acid supplementation for the patients with FRα defect normalized CSF 5-MTHF (>25 nmol/L) and resulted in clinical improvement. Although folic acid therapy for the patient with KSS moderately increased CSF 5-MTHF (22.7 nmol/L), the patient with MTHFR deficiency showed no increase in 5-MTHF.
[Conclusions] The assay of 5-MTHF is helpful in the diagnosis and evaluation of treatment in CFD and 5-MTHF biosynthesis defect.